Delta-Aminolevulinate synthase and delta-aminolevulinate dehydratase activities were determined in liver biopsy specimens obtained from 12 patients with hepatic cirrhosis. Delta-Aminolevulinate synthase activity was determined by the incorporation of [1,4-14C]succinyl coenzyme A into delta-aminolevulinate. The mean activity of delta-aminolevulinate synthase was significantly higher in cirrhotic liver specimens (mean +/- SE, 193.7 +/- 34.5 picomoles delta-aminolevulinate per milligram protein per 30 minutes) than in controls with minimal histologic changes (32.7 +/- 13.6, p less than 0.01). Furthermore, the mean activity of delta-aminolevulinate synthase was higher in micronodular cirrhosis (281.6 +/- 58.8) than in the other types of cirrhosis (131.0 +/- 23.1, p less than 0.05). Levels of indocyanine green retention at 15 min correlated with the activity of hepatic delta-aminolevulinate synthase (p less than 0.05). The mean activity of delta-aminolevulinate dehydratase, in contrast, was significantly lower in cirrhotic liver specimens (9.4 +/- 1.3 nanomoles porphobilinogen per milligram protein per hour) than in controls (22.0 +/- 2.6, p less than 0.05). These results suggest that the extent of liver injury or the degree of portosystemic shunting, or both, influence the rate of hepatic heme biosynthesis.