There are no well-established modifiable risk factors for pancreatic cancer except smoking. Some dietary factors have been associated with pancreatic cancer risk and require further study. We examined the associations among intake of specific fatty acids and antioxidants and risk of pancreatic cancer in a large population-based case-control study in the San Francisco Bay Area. Unconditional logistic regression models were used to compute odds ratios (ORs) and 95% confidence intervals (CI) as estimates of relative risk. Positive associations were observed for high levels of the 8 individual saturated fatty acids (4th vs. 1st quartile: ORs ranged from 1.6 to 2.6; all p(trend) < 0.01), monounsaturated palmitoleic and oleic fatty acids [OR = 1.6 (95% CI: 1.2-2.1) and 1.4 (95% CI: 1.1-1.9); both p(trend) < 0.01], and polyunsaturated linolenic acid [OR = 1.5 (95% CI: 1.1-2.0); p(trend) = 0.02]. Inverse associations were observed for high levels of gadolic acid [4th vs. 1st quartile: OR = 0.68 (95% CI: 0.50-0.92); p(trend) = 0.007] and omega-3 fatty acids [>or=0.85 g/day vs. 1st quartile: OR = 0.47 (95% CI: 0.25-0.90)]. An inverse association was also observed for high total intake of vitamin C [4th vs. 1st quartile: OR = 0.69 (95% CI: 0.51-0.94); p(trend) = 0.004] and of vitamin E [OR = 0.67 (95% CI: 0.49-0.92); p(trend) = 0.01]. Although similar decreased risks were also observed for high supplemental intake of these 2 vitamins (both p(trend) < 0.01), no association was observed for intake from food alone. These results support the hypotheses that a high intake of saturated and certain monounsaturated fatty acids may increase the risk of pancreatic cancer, whereas greater intake of omega-3 fatty acids, vitamins C and E may reduce the risk.