Acute but not delayed nausea is well controlled by serotonergic receptor-antagonists implicating different mediation of delayed as compared to acute nausea and vomiting. We report on differences in central neural activity using positron emission tomographic (PET) measurements of regional cerebral blood flow (rCBF) in two chemotherapy treated cancer patients during delayed severe and mild nausea. Subtractive image methodology where rCBF during moderate nausea was subtracted from rCBF during mild nausea revealed increased neural activity in the anterior hypothalamus, the vermis, the anterior cingulate gyrus and the thalamus as well as decreased activity in the pens and the substantia nigra. These results may reveal central nervous system substrates underlying delayed nausea and vomiting and are consistent with an interpretation in terms of activation both of serotonergic and noradrenergic but not dopaminergic transmitter systems. It is concluded that noradrenergic mediation of delayed nausea is not an unlikely possibility.