The afferent connectivity to the primary olfactory cortex (POC) from the olfactory bulb is ipsilateral in humans and other species [1]. The POC itself is not a unitary structure, but rather a collection of brain regions including the piriform cortex and amygdala, insula, and orbitofrontal cortex [1]. Interhemispheric connections exist via the anterior commissure [1] and other downstream structures, suggesting that direct olfactory sensory processing is unilateral, while some secondary olfactory processing occurs bilaterally. In addition, POC activity is increased by olfactory motor behavior (i.e., sniffing) compared to normal breathing [2], even in the absence of an odorant. In this study we administered monorhinal (only one nostril) and dirhinal (both nostrils) olfactory stimulation to determine whether sensory receptor laterality determines lateralization of neural activity in regions of the POC, and whether this is altered by sniffing (3). We expected lateralized stimulation to produce lateralized activation, and that sniffing would enhance activation bilaterally.Twenty normosmic (N=20) subjects (males/females) completed an olfactory fMRI paradigm with four conditions: 1) dirhinal PEA; 2) dirhinal air; 3) monorhinal PEA left; and 4) monorihinal PEA right. Each condition was presented 6 times with an inter-trial interval of 24 seconds to prevent habituation. There were 6 trials of each type for a total of 24 trials. The odorant was PEA (i.e., the smell of a rose). There was a constant flow rate of fresh air/odorants (8L/min). The task was performed passively; no response was required. Each subject performed the task twice, with instructions to either ‘Sniff’ when cued, or ‘No sniff, breathe normally.’Data were analyzed with a boxcar convolved with a hemodynamic response function within the GLM in SPM8, and indicate a mix of expected and unexpected results that are in agreement across the two ‘Sniff’ and ‘No sniff’ conditions. For the “Sniff” paradigm, monorhinal and dirhinal stimulation elicited activation in the POC (Figure 2), as in the ‘No sniff’ condition (Figure 3). Our results for the ‘Sniff’ condition (Figure 2) show that stimulation to the right nostril activated only the right piriform cortex unilaterally, while left stimulation activated the piriform cortex bilaterally, similar to dirhinal stimulation. For the “No sniff” paradigm, results replicated the “Sniff” condition: monorhinal and dirhinal stimulation elicited activation in the POC (Figure 3). Stimulation to the right nostril activated only the right piriform cortex unilaterally, while left stimulation activated the piriform cortex bilaterally, again similar to dirhinal stimulation. Sniffing had no effect on bilateral activation in either of the unilateral stimulations.Our results show mixed effects concerning laterality of stimulation and activation. When olfactory stimulation is unilateral, the right POC responds more vigorously than the left POC, regardless of the nostril that was stimulated. When olfactory stimulation is bilateral, or when there is no odor present, POC activation is bilateral. Our findings are in line with previous studies that suggest asymmetry in both the POC and orbitofrontal cortex depending on olfactory task demands[4].The simple olfactory fMRI paradigms provided a straight forward method to obtain information about nostril specific processing in the brain.