There are conflicting data in the literature regarding the role of monamines in the secretion of insulin. In order to clarify the contribution that species variation may make to these divergent results, the uptake of serotinin (5-HT), dopamine (DA), and their precursor amino acids, 5-hydroxytryptophan (5-HTP) and L-dopa, into islets was studied. Islets from golden hamsters, rabbits, guinea pigs, and obese, hyperglycemic mice were isolated by the collagenase technique. The islets were incubated in Krebs-Ringer buffer in the presence of 14C-labeled monamines or their precursors. At 30-minute intervals after initiating the study, the incubation mixture was passed through a Millipore filter. The retained islets were disrupted by sonication and the radioactivity counted. The ratio of the uptake of 5-HTP to 5-HT was at least 3:1 in the hamster, guinea pig, and mouse. In the rabbit the ratio was 1:1. A similar relationship was noted for the uptake of L-dopa and DA. The in-vitro results were confirmed by the in-vivo studies, in which hamsters were injected with 14C5-HT or 5-HTP, followed by isolation of the islets. We conclude that there is significant species variation inthe uptake of these monoamines and their precursors.