Summary. In an attempt to study the influence of seminal prostaglandin reduction on male fertility, the effect of prolonged treatment with 4 non-steroidal anti-inflammatory drugs (acetylsalicylic acid, indomethacin, naproxen and phenylbutazone) on fertility was determined in male rats. Before the fertility experiments, the pharmacokinetics of the drugs were determined to find dosage regimens by which drug concentrations known as active from human anti-inflammatory therapy could be reached and maintained in the animals. Except for phenylbutazone, all drugs decreased prostaglandin E-2 level in seminal fluid by 80–90%, but only indomethacin reduced fertility significantly. The results suggest that reduction of prostaglandin synthesis in male rats does not affect fertility, which might be related to the very low seminal prostaglandin levels in rats compared to those in animals of other species.