Background Clinical experience of cases of fatty liver disease (FLD) with exposure to organic solvents suggested a possible risk. Methods Thirty male cases of FLD, ages 20-59 years, with biopsy records at departments of pathology in southeast Sweden were compared to 120 male controls randomly drawn from the study area population. Questionnaire information was obtained about job titles and specific occupational exposures; exposure level categories were then assessed blindly for both cases and controls. Medical records for cases were scrutinized to elucidate possible confounding and/or interacting effects from alcohol, the use of drugs, and other diseases. Results Moderately intense and mixed solvent exposure for more than 1 year within the last 15 years prior to diagnosis resulted in an age-adjusted Mantel-Haenszel odds ratio of 4.3 (95% confidence interval (CI), 1.2-15); for intense exposure, the odds ratio was 7.7 (95% CI 1.7-48). Confounding from alcohol, use of drugs, other diseases, and overweight could be ruled out with reasonable confidence. Conclusions This study indicates that occupational exposure to organic solvents may play a role in the development of FLD, as indicated earlier in case reports and in one small case-control study.