Among the subjects enrolled in the American Cancer Society Cancer Prevention Study II, a large nation-wide prospective study, 282 died from multiple myeloma (MM) during the first 4 years of follow-up. These were divided into incident cases who were initially free from disease and prevalent cases who reported MM or related symptoms at the time of enrollment. For each case, 4 controls matched for age, sex, ethnic group and residence were randomly selected. Previous history of diabetes [odds ratio (OR) = 2.0] and employment as farmer (OR = 2.7) were the risk factors consistently suggested by the results of the analysis. The risk associated with farming showed a linear trend with duration of exposure. Pesticide or herbicide exposure was not a risk factor per se but, when combined with farming, it increased the OR to 4.3. Low education, occupational exposure to dyes, and employment in a bank, on the railroad or as a maid were also suggested risk factors, but either they were not statistically significant or they were based on small numbers of exposed subjects. No association between MM and asbestos exposure was observed.