To determine the effects of peptide 6A (a fibrinogen-degradation product) on femoral blood flow, anaesthetized dogs were given saline or peptide 6A intravenously in random order. Bolus injection of peptide 6A (10, 20 or 50 mumoles) caused a short-lasting dose-dependent decrease in femoral bed resistance and an increase in femoral blood flow. Continuous infusion of peptide 6A (50 mumoles min-1) resulted in a sustained decrease in resistance and an increase in femoral artery blood flow (54 +/- 33%), with a small, insignificant decrease in femoral artery mean pressure. Indomethacin pretreatment caused only slight attenuation of the peptide 6A-induced increase in femoral blood flow. In in vitro experiments, peptide 6A relaxed rings of femoral artery, and this effect was associated with an increase in 6-keto-PGF1 alpha in the vascular ring supernatants and in the tissue cyclic GMP concentrations. Peptide 6A-induced relaxation was abolished by de-endothelialization, but not by treatment with indomethacin. These observations suggest that peptide 6A induces vasorelaxation largely by stimulating release of endothelium-derived relaxing factor. PGI2 release appears to play only a minor role in the vasodilator effects of peptide 6A in the femoral bed.