A protein meal is well known to induce a prompt secretion of insulin and glucagon. However, the data regarding the dose-response relationship between he protein meal and the insulin and glucagon responses are sparse. This study assessed the effects of ingestion of protein meals of varying amounts on plasma glucose [S], insulin [I], and glucagon [G] concentrations in eight normal subjects. Protein meals were administered after an overmight fast in a randomized sequence at intervals of 10 days in four different quantities: 250 mg/kg body weight (BW) (A), 500 mg/kg BW (B), 1 g/kg BW (C), and 2 g/kg BW (D). Mean S levels were not significantly altered following A, B, or C, although significant decreases in S responses were noted after C and D as reflected by absolute changes (Δ) and/or the cumulative responses (CR) and the areas under the curve (Σ). Mean I increased promptly to peak concentration by 30 minutes, although in individual subjects the peak was achieved either at 30 or 60 minutes following all protein meals. The increase was progressively greater and the return was delayed with increasing quantities resulting in progressive elevations in ΔI and percent increase from basal concentration (%), as well as CRI and ΣI. G increased following all protein meals as well. The mean peak G concentrations were achieved by 90 minutes, although in individual subjects the peak G was reached at 90 or 120 minutes, a significant delay in comparison to the peak I levels. G returned to base line only following ingestion of A during the study period. Furthermore, the ΔG, %G, CRG, and ΣG responses increased progressively with the quantities of protein meal reaching maximum following C with no further significant change with D. Finally, I G molar ratios increased from the basal levels following all meals and the rise was progressively higher with increasing quantities. Therefore, this study demonstrates that even a small protein meal is an effective secretogogue for pancreatic α and β cell with somewhat dissimilar dose-kinetics. Moreover, β cells appear to be more responsive than α cells. It is also apparent that increasing I G ratios with the increasing quantities of protein meals may be responsible for the decline in glucose concentration noted on ingestion of larger protein meals. © 1991.