Hepatic function was assessed in 13 healthy elderly subjects, 71-88 years of age, with three quantitative tests of liver function. The galactose elimination capacity was significantly (P less than 0.05) lower in the elderly (6.08 +/- 1.30 mg X min-1 X kg-1, mean +/- SD) than in a group of 70 subjects under 40 (7.48 +/- 0.94 mg X min-1 X kg-1) and 11 subjects between the age of 40 and 70 (7.08 +/- 0.68 mg X min-1 X kg-1). The demethylation of aminopyrine as assessed by the aminopyrine breath test, and the systemic clearance of caffeine, two measures of microsomal function, demonstrated a comparable decrease but showed much more interindividual variation. Caffeine clearance decreased from 1.49 +/- 0.44 ml X min-1 X kg-1 in young adults to 0.97 +/- 0.39 ml X min-1 X kg-1 (P less than 0.01) in the elderly, and the demethylation of aminopyrine decreased from 0.79 +/- 0.15 to 0.62 +/- 0.20% dose X kg X mmol-1 (P less than 0.05). Our data indicate that aging is associated with a loss of the functioning mass of hepatocytes. The decrease in drug metabolism parallels the loss of functional mass but shows more interindividual variation probably reflecting the many genetic and environmental factors influencing these tests of microsomal function.