Genetic polymorphisms may explain why certain individuals will develop exertional rhabdomyolysis (ER) or markedly elevated serum creatine kinase (CK) levels following exertion, while others in the same environment, performing the same exertion, do not. Prospectively, 499 recruits were evaluated during the initial fortnight of Army basic training. Serum CK levels were determined before and during that time. Eleven candidate genetic polymorphisms were studied and compared to CK levels. No subjects developed ER. Baseline CK was significantly greater in interleukin-6 G174C GG and myosin light chain kinase 2 (MLCK 2) AA subjects. Intertraining levels were significantly greater in angiotensin I-converting enzyme D/D and interleukin-6 GG subjects. Among African-Americans, those with MLCK2 AA had greater baseline CK (1,352 +/- 1,102.8 IU/L) than AC and CC genotypes (536.9 +/- 500.6). African-American men have the highest baseline levels and are more likely to have MLCK AA genotype. Whether this finding is associated with an increased incidence of ER requires further study.