In 188 patients from separate families with various forms of retinitis pigmentosa (RP) and 91 normal subjects, plasma fatty acids were measured as a percentage of total plasma fatty acids, and their concentrations were determined using capillary-column gas-liquid chromatography. After controlling for the effects of age and gender, those with RP had significantly lower (P less than 0.01) mean plasma percentages and concentrations of the omega-3 fatty acids: 18:3 omega 3 (alpha-linolenic acid), 22:3 omega 3 (13,16,19 docosatriaenoic acid), and 22:6 omega 3 (docosahexaenoic acid, DHA) compared with the group of normal subjects. The mean percentages were reduced 15%, 14%, and 10%, respectively, below the mean percentages in normal subjects. Analysis by genetic type revealed that the X-linked and isolate forms of RP had significantly lower (P less than 0.01) mean percentage values for DHA (18% and 17%, respectively). Dominant and recessive forms of RP had DHA levels close to normal. Mean absolute plasma DHA concentrations in X-linked RP were not significantly different from the concentrations in the control subjects, although these levels were significantly lower in patients with isolate RP. These data identify the possibility that some forms of RP may have alterations in plasma omega-3 fatty acid metabolism resulting in decreased plasma DHA content. These observations await additional confirmation using an analysis of the fatty acid content of specific erythrocyte phospholipid classes.