Green sunfish (Lepomis cyanellus) were injected daily with either murine leptin, phosphate-buffered saline (PBS), or simply handled without injection for 14 days. At the end of the experiment, fish were assayed for intracellular indicators of fatty acid metabolism. Intracellular fatty acid-binding protein (FABP) expression in heart ventricle was twofold higher in the leptin treated group (87.2+/-5.6 Leptin; 47.2+/-6.8 PBS; 28.9+/-3.9 Handled; percent relative expression, Prob.>F<0.001). Two other indicators of intracellular fat metabolism, carnitine palmitoyl transferase activity (CPT) in liver and 3-hydroxyacyl-CoA dehydrogenase (HOAD) in heart were not significantly different among groups, although the trend is for higher values in the leptin treatment (CPT: 0.23+/-0.04 Leptin, 0.11+/-0.04 PBS, 0.10+/-0.03 Handled; U/gm wet weight; Prob.>F=0.08; HOAD: 1.34+/-0.28 Leptin, 0.76+/-0.12 PBS, 0.86+/-0.25 Handled; U/gm wet weight; Prob.>F=0.18). Percent change in total weight, body fat (as a percent of dry weight), cardiosomatic index, and hepatosomatic index were not significantly different among treatments. These results suggest that fish respond to murine leptin injections by increasing fat metabolism, however many of the hallmarks of leptin treatment in mammals (loss of total weight and body fat) were not observed. This lack of response may be due to incompatibility of mouse leptin with fish receptors or an inadequate dose of leptin. We also suggest that leptin's action may be slower in ectotherms due to their lower metabolic rate.