To determine the effect of insulin and glucagon on the transformation of nonesterified fatty acids (NEFA) into ketone bodies (KB), we measured simultaneously in normal subjects NEFA and KB kinetics at different NEFA levels in the presence of basal (control test) or increasing insulin concentrations with glucagopenia (somatostatin + insulin infusion, insulin test) and without glucagopenia (somatostatin + insulin + glucagon infusion, glucagon test). NEFA levels were controlled during these tests by an intravenous (IV) infusion of a triglyceride emulsion. During the control test, a moderate increase of NEFA (464 +/- 30 to 715 +/- 56 mumol/L) increased the percentage of NEFA converted into KB (13.3% +/- 1.4% to 26.4% +/- 2.1%, P less than .05), and there was a linear relationship between this percentage and NEFA levels (r = .788, P less than .01). During the insulin and glucagon tests, the progressive increase in NEFA induced by the triglyceride emulsion infusion was associated, despite the increase of insulinemia, with an increase in KB production rate (P less than .05) and in the proportion of NEFA used for ketogenesis in the presence (8.1% +/- 1.2% to 14.2% +/- 6.3%, P less than .05) and absence (15.7% +/- 2.8% to 25.2% +/- 3.99%, P less than 0.05) of glucagopenia. In both tests, this percentage was always linearly related with NEFA levels (P less than .05) and the slopes of these relationships were comparable to that observed in the control test. However, the fraction of NEFA used for ketogenesis was always higher (P less than .05) during glucagon substitution than in its absence.(ABSTRACT TRUNCATED AT 250 WORDS)