This study was designed to investigate the effects of dietary modification of prostaglandin (PG) synthesis on blood pressure regulation in spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats under conditions of normal and elevated salt intake. Forty rats from both strains were placed on either a two-series PG inhibitory diet of Max eicosapentaenoic acid (EPA) fish oil or a control diet of saturated fat for an initial period of 4 weeks. The groups were then divided into two, so that half of each received 1.5% saline in place of their drinking water for 1 week. Blood pressure of the SHR and WKY were unaffected by dietary fat before the addition of saline, but with salt loading, the Max EPA-fed SHRs showed a mean blood pressure increase of 21 mmHg relative to the EPA-fed SHR with access to water. Rats fed EPA showed impaired ability to generate serum thromboxane (TXB2) and in the groups with access to water, diminished excretion of urinary 6-keto-PGF1 alpha and PGE2. Salt loading increased prostanoid synthesis and excretion. Spontaneously hypertensive rats had greater serum TXB2 generating capacity than WKYs, but diminished urinary PGE2 excretion in those animals with access to water. The increased blood pressure observed in the salt-loaded SHR on the Max EPA-diet may be explained by reduced PG synthesis resulting in either mild sodium retention and/or increased vascular reactivity.