Serum enzyme alterations in chronic muscle disease. A biopsy-based diagnostic assessment. The results of interpretation of muscle biopsies were compared retrospectively to activities of serum enzymes and isoenzymes. A total of 137 patients seen at the Cleveland Clinic Foundation in 1986 and 1987 were included in this study. Serum enzymes evaluated were CK, AST, LD, and aldolase (ALS), as well as the percentage CK-MB isoenzyme. The units of CK-MB and the ratios of CK to AST, LD, and ALS were calculated. Descriptive statistics, Kruskal-Wallis one-way analysis of variance, and stepwise logistic regression were performed. A diagnostic algorithm was constructed using a computer-assisted rule generation program. Myopathic diseases yielded a greater mean increase in serum enzyme activity than atrophic diseases. By multivariate stepwise logistic regression, increases in serum AST and CK activity were independently associated with the presence of inflammation in a muscle biopsy specimen. The diagnostic algorithm allowed for the separation of myopathies from atrophies and could identify cases of Duchenne's muscular dystrophy and polymyositis. 