Many psychiatric patient groups smoke heavily, but little is known regarding the effects of this habit on functional brain imaging results. The present report assesses the effect of chronic smoking on the blood oxygen level-dependent (BOLD) response to a simple visual activation (VA) task and a breath hold (BH) task in patients with schizophrenia. Eight healthy controls and twelve patients with schizophrenia were studied. Half of each group had never smoked and the other half of each group had smoked for more than 10 pack years. Responses to the VA task were assessed in the visual cortex and responses to the BH task were assessed in gray matter generally. There were four fMRI-dependent measures: (1) median percent signal change; (2) activation volume (in voxels); (3) time-to-peak of the impulse response function (IRF); and (4) time-to-trough of the IRF. All measures were tested as dependent variables in an ANCOVA with diagnosis and smoking status as crossed factors and age as a covariate. Heavy smokers had 22% larger percent signal change for the VA task and 50% larger percent signal change for the BH task. Patients had a 40% larger percent signal change for the breath hold task. Other statistically significant effects of smoking history on activation volume and the timing of the brain responses were noted. If replicated, the results may have important implications for fMRI studies comparing groups with markedly different smoking habits, such as studies comparing patients with schizophrenia, 60-90% of whom smoke, and healthy controls, who smoke with a much lower frequency.