H2-receptor antagonists differentially inhibit cytochrome P450 and this may affect the rate at which benzodiazepines are metabolised. However, it is not known whether this delayed clearance results in prolonged psychomotor impairment. In a randomised double-blind trial 28 healthy volunteers received two single doses of midazolam (0.07 mg.kg-1) at an interval of one week during which they took cimetidine 400 mg, ranitidine 150 mg or placebo, each twice daily. Recovery from the benzodiazepine was monitored on each occasion over a 12 h period using a battery of psychometric tests. There was wide individual variation in performance; however, an overall measure of impairment indicated a significant difference at 2.5 h (p < 0.05), the cimetidine group having a high impairment score. This decrement appeared to be in cognitive and psychomotor functions and was not reflected in the subjective assessment.