The effects of diazepam on optokinetic nystagmus (OKN) eye movements were studied under closed-loop and open-loop conditions in healthy humans. The open-loop condition was achieved by adding the eye-movement velocity signal of OKN to the computer-generated signal controlling the moving stimulus grating. Each of four subjects received a single oral dose of 5 mg diazepam or a placebo on two separate days in a double-blind randomized fashion. OKN eye movements were measured 90 min after administration of the treatments. As compared to placebo, diazepam significantly reduced the gain of open-loop OKN, but did not modify the gain of closed-loop OKN. The results indicate that the OKN gain under the open-loop condition is a more sensitive detector of the parameter changes of the OKN system than under the closed-loop condition. Thus, open-loop OKN gain can provide an objective, quantitative measure of benzodiazepine agonist effects.