Fish oils are abundant in polyunsaturated fatty acids of the n-3 series (in particular eicosapentaenoic, 20:5 and docosahexaenoic acid, 22:6). Such fatty acids are generally considered to be beneficial in the prevention of cardiac disease and to have anti-inflammatory properties. Neutrophil adherence is an essential early event in an acute inflammatory response, and we have demonstrated that both 20:5 and 22:6 stimulate adherence in vitro. Arachidonic acid (20:4, n-6) was also stimulatory. Significant simulation of adherence was seen from 5 to 80 microM (nontoxic concentrations) 22:6, 20:5, or 20:4. At the lower fatty acid concentrations tested (< or = 40 microM) 20:5 was less active than 22:6 or 20:4 at stimulating adherence. Above 40 microM there was no difference in the ability of the three fatty acids to stimulate adherence. At the lower fatty acid concentrations tested (< or = 10 microM) 22:6 was less active than 20:4, whereas above 10 microM they were equally active. Immunofluorescent flow cytometric analysis of neutrophil integrin (adherence) receptors showed that the complement C3bi receptor (CD11b) was up-regulated by these fatty acids. There was no change in CD11a or CD11c. Saturated fatty acids of the same chain length were without effect on adherence or receptor expression. The findings suggest that these polyunsaturated fatty acids may, under certain conditions, be proinflammatory with respect to their acute effects on the interaction of neutrophils with microbes, endothelium, and other tissues.