Following injection of histidine (as 1-histidine monohydrochloride, 500 mg/kg, IP) rats showed a suppression of total food intake within the first 2 hours of a 12 hour daily feeding period but not if the rats were adapted to a 4 hour daily feeding period. Furthermore, rats adapted to a nocturnal as compared to a diurnal 12 hour feeding period showed a greater response (50% vs. 20% suppression of feeding) to histidine. Overall, within an experiment, food intake suppression correlated with the histidine dose (0, 125, 250, 375 and 500 mg/kg; for mean response r(3) = 0.90, p less than 0.05) although the lowest dose measured to be effective in a cross-over design experiment was 375 mg/kg. No differential effect upon protein or carbohydrate intake was observed in any of the studies. The effects of injections of 250 and 500 mg/kg histidine on food intake were associated with significant elevations of brain histidine and histamine. We conclude that histidine, possibly by changes in brain histidine, influences total food intake but not macronutrient selection.