Regulatory effects of carnitine, glucose, some glucogenic compounds (propionate, pyruvate, alanine, lactate, glycerol, and fructose), ketone bodies (acetate, acetoacetate, and beta-hydroxybutyrate), and insulin on oxidation of palmitate were studied in slices of liver obtained from high producing dairy cows during early lactation. A total of 77 biopsies of liver from 21 multiparous Holstein cows (36 +/- 16 d postpartum) was used. L-Carnitine increased oxidation of palmitate to CO2 by more than twofold and oxidation to acid-soluble products by about fourfold. Propionate decreased oxidation of palmitate in liver slices incubated without added carnitine, but the decrease was lessened by carnitine. Pyruvate, lactate, and alanine increased palmitate oxidation, especially in the presence of carnitine. Glycerol, glucose, and insulin tended to decrease palmitate oxidation in the absence of carnitine. Fructose tended to decrease oxidation to CO2 but did not affect oxidation to acid-soluble products. Acetate and acetoacetate decreased oxidation of palmitate, whereas beta-hydroxybutyrate decreased palmitate oxidation in the absence of carnitine but increased palmitate oxidation in its presence. In general, carnitine decreased the inhibitory effects of compounds that decreased palmitate oxidation but increased the stimulatory effects of compounds that increased palmitate oxidation.