Hepatic and alimentary ketogenesis occur at similar rates in fed, nonpregnant, nonlactating goats, sheep and dairy cows. Alimentary ketogenesis begins to diminish within 24 h after fasting but compensatory increases in hepatic ketogenesis maintain total splanchnic release and, therefore, no change in circulating concentrations of ketone bodies is observed. By the third day of fast the gut is utilizing acetoacetate and beta-hydroxybutyrate and alimentary ketogenesis has ceased. Hepatic ketogenesis of both ketone bodies accelerates rapidly due to portal-drained visceral and hindquarter lipolysis and subsequent hepatic fatty acid uptake and total circulating concentrations are doubled. During pregnancy and lactation in sheep and cows alimentary ketogenesis is maintained as long as digestible organic matter intake is constant. Hepatic and total splanchnic release of beta-hydroxybutyrate increases in late gestation and early lactation. Again, this is due to increased portal-drained visceral and hindquarter free fatty acid release and hepatic free fatty acid uptake. Hindquarter uptake of both ketones during late gestation is similar to the ratio observed in nonpregnant fed sheep but the percentage of utilization decreases, perhaps reflecting partitioning to uteroplacental tissues. Hindquarter uptake of both ketone bodies in sheep increases in early lactation due to increased circulating concentrations because extraction ratios are similar to those of fed animals. Ketosis during pregnancy in sheep and lactation in cows may be prevented by beta-hydroxybutyrate stimulation of pancreatic insulin production. However, an insulin-independent intrahepatic mechanism apparently occurs in sheep.(ABSTRACT TRUNCATED AT 250 WORDS)