The efficacy and tolerability of nefazodone in the treatment of major depression among Spanish-monolingual Hispanics was examined and compared to historical controls among English-speaking, predominantly non-Hispanic subjects. Fifty monolingual Hispanic outpatients with major depression and a HAM-D17 score > or = 18 were treated with nefazodone in a flexible-dose 8-week open-label protocol. Sixty-three percent of the intent-to-treat (ITT) sample with > or = 1 efficacy visit were considered responders according to CGI-I criteria, falling within the range of response rates (58-69%) reported in six prior nefazodone trials with non-Hispanic subjects. Significant improvement was found for the ITT and completer samples in HAM-D17, HAM-D28, and SCL-90 scores and in two measures of psychosocial functioning. Endpoint mean dose in the ITT sample was 379 mg/day (SD = 170), also within the range of previous trials (321-472 mg/day). Adverse effects were not elevated, with only dry mouth (8%) reported by > 6% of subjects. However, 42% of the sample dropped out of treatment before study termination, usually because of side effects or due to family or work difficulties, a higher rate than previously reported for nefazodone (21-33%). This open trial finds nefazodone to be an efficacious treatment for major depression among monolingual Hispanics, with comparable efficacy to previous controlled trials among non-Hispanic subjects. Double-blind studies are required to confirm this comparable efficacy. Mean endpoint doses and adverse effect rates similar to previous trials do not support the need for reduced doses of nefazodone among Hispanics. However, an elevated rate of treatment discontinuation threatens treatment efficacy among this population. Causes for this elevated rate require explanation, given the apparently unremarkable pattern of adverse effect reports.