We have analyzed the usage pattern of valproate and the associated hepatic fatalities that have been reported in the 2 years since our first study evaluating US experience during the period 1978-1984. In this follow-up study (1985-1986), we have observed a nearly fivefold decrease in the incidence of hepatic fatality during a time when the overall use of valproate has increased significantly. The dramatically decreased incidence, from 0.93 per 10,000 (1/10,000) in 1978-1984 to 0.20 per 10,000 (1/49,000) in 1985-1986 appears to be due to changes in the prescribing patterns of physicians, prompted by greater awareness of low-risk versus high-risk patients. More patients are receiving valproate as monotherapy, considerably more low-risk patients are being treated with valproate, and fewer high-risk patients (0 to 2 years old) are being treated with valproate. During 1985-1986, no hepatic fatalities were reported in any patients above the age of 10 years, regardless of whether valproate was administered as monotherapy or polytherapy. The altered exposure pattern, with an increased use of monotherapy, appears to have had a positive impact on the number of hepatic fatalities (four among 198,000 patients treated during 1985-1986) and contributed to a decreased rate of valproate-associated hepatic fatality.