Some researchers have hypothesized that omega-3 fatty acids, found primarily in fish oils, may protect against the development of rheumatoid arthritis. We conducted a population-based case-control study in women, comparing 324 incident rheumatoid arthritis cases with 1,245 controls. We used a food frequency questionnaire to ascertain diet during a 1-year period 5 years before a reference date (first physician visit for joint-symptoms). Consumption of broiled or baked fish, but not of other types of fish, was associated with a decreased risk of rheumatoid arthritis. The adjusted odds ratios (OR) for 1- < 2 servings and > or = 2 servings of broiled or baked fish per week, compared with < 1 serving, were 0.78 [95% confidence interval (CI) = 0.53-1.14] and 0.57 (95% CI = 0.35-0.93). Other analyses showed associations with protein as a percentage of calories (adjusted OR for the top quartile as compared with the bottom quartile = 0.65; 95% CI = 0.46-0.94) and total calories (adjusted OR for the top quartile = 1.62; 95% CI = 1.15-2.28). The associations with broiled or baked fish, protein, and calories became stronger when we restricted our analysis to cases positive for rheumatoid factor. These results support the hypothesis that omega-3 fatty acids may help prevent rheumatoid arthritis.