Data from 83 nurses and pharmacists handling antineoplastic drugs and 35 nurse/pharmacist controls who participated in a national study of antineoplastic drug-handling risks were examined to investigate antineoplastic drug exposure. Measures of external exposure included self-completion drug logs and industrial hygiene scans conducted in clinical settings. Internal exposure was measured by urine mutagenicity tests on end-of-week 24-hour urine specimens. To control for potential confounders, the staff was asked to complete food and hobby diaries and to avoid identified mutagenic substances for 1 week before collection of 24-hour urine samples. On the scans of the drug handlers, 13% showed one or more spots of drug contamination on gloved and ungloved hands, gowns, or shoes. Of the 24-hour urine samples, 15% were mutagenic for Salmonella typhimurium: Rates did not differ significantly for drug handlers and controls. Among nurses who both prepared and administered antineoplastics, those with positive mutagenicity tests handled more doses of the drugs, used less skin protection, and had more skin contact with the drugs than those with negative tests. Nurses who only administered the drugs and had positive mutagenicity tests handled fewer doses of drugs than those with negative tests, but they also reported less use of protection and more skin contact. For both groups of nurses, skin contact with antineoplastics was associated with positive mutagenicity test results (p < 0.01).