The effects of work related exposure to compounds contaminated with 2,3,7,8-tetrachloro-dibenzo-p-dioxin (1746016) (TCDD) on cytochrome- P450 activity were examined in a medical survey. The cohort included 58 TCDD exposed workers (age range 31 to 77 years) from two chemical factories involved in the manufacture of 2,4,5- trichlorophenol. TCDD exposure was suspected to have occurred between 1951 to 1969 and 1968 to 1972. A referent group of 125 unexposed community residents was included. Urine samples were collected from the exposed workers for an analysis of caffeine metabolism and serum TCDD measurements. Cytochrome-P450 activity was assessed in the ratio of caffeine metabolites (CMR). Since smoking could also be a cytochrome-P450 inducer, urinary cotinine measurements were also conducted. Samples were quantified by high performance liquid chromatography. Comparison of control and exposed data revealed nonsignificant relationships for three of the four TCDD exposure level categories. No association between serum TCDD and cytochrome-P450 induction was observed as evaluated by CMR. A strong correlation was observed between enzyme induction, as quantified by CMR, and smoking, as quantified by urinary cotinine. The authors conclude that the small size of the study, insensitivity of CMR assessments, and low levels of TCDD exposure may contribute to the lack of correlation between serum TCDD and cytochrome-P450 activity.