Reports concerning changes in plasma neurotransmitter values that result from dietary manipulations have not been published so far. The influence of various meal compositions on platelet-poor plasma (PPP) serotonin (5-HT) and norepinephrine (NE) levels was investigated. Healthy volunteers were subjected to three test meals: a carbohydrate-rich meal (86% carbohydrates), a protein-rich meal (70% protein), and a fat-rich meal (92% fat). After a carbohydrate-rich meal, PPP 5-HT values increased significantly (4.47-fold, P less than .02), whereas a smaller increase (1.66-fold, P = NS) was observed after a fat-rich meal. These effects on PPP 5-HT values could be correlated with insulin plasma levels. A protein-rich meal significantly reduced (P = 0.0011) PPP 5-HT to 28% of initial values, despite an increase in plasma insulin levels. This study has shown that (1) changes in meal compositions influence PPP 5-HT and, to a lesser extent, NE values; (2) the resulting changes in PPP 5-HT levels parallel those reported for brain neurotransmitters; and (3) these results seem to indicate that PPP 5-HT levels may be a model for brain synthesis and release of 5-HT.