A 38-year-old female was drinking 30 drinks/week before entering a 12-week, double-blind study of nalmefene for the treatment of alcohol dependence. Liver function tests (LFTs) were within normal limits at baseline and week 4, but on week 8, the ALT showed a 7-fold increase, and the AST showed a 4-fold increase from baseline. A decision was made to continue study medication based on the patient's positive response to this therapy (i.e., achieving complete abstinence) and no known dose-dependent association with liver toxicity in over 1300 patients treated with nalmefene for other indications. LFTs were repeated serially to assess the trend of the LFT values. The patient achieved total abstinence over the course of the study period and at the 3-month posttreatment follow-up was continuing to maintain these gains from the study program, and her LFTs had returned to normal. A gradual return to normal in ALT and AST, while treatment with nalmefene continued, does not support the role of nalmefene as an hepatotoxin. Relapse to drinking was excluded because of normal values for the gamma-glutamyltransferase, and verification of sobriety by self-report, significant other, and breathalyzer. A virology panel ruled out the presence of viral hepatitis. Dietary intake before the elevation in LFTs contained elements that have established association with hepatocellular changes. The routine prescription of serial LFTs in alcoholism pharmacotherapy trials may be expected to reveal clinically nonsignificant elevations that could potentially be related to exogenous factors, such as dietary composition and should not be reflexively attributed to medication under investigation and/or drinking.