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The increments in serum lactate and ketone bodies induced by biguanides in 11 diabetics were decreased by a combined treatment with clofibrate and phenformin. Lactate concentration was nearly the same on a placebo or on the combined drug treatment. While-body weight reduction in subjects was without influence on the clofibrate-induced lowering of lactate it inhibited a decrease of ketone bodies. The effect of clofibrate on lactate was directly correlated to its serum triglyceride lowering effect. The decrease in lactate points to an improved lactate utilization. A combined clofibrate-biguanide treatment is only indicated in selected patients, predominantly in diabetics with endogenous hypertriglyceridemia, however, contraindications of both drugs have to be observed.