The aggregation response of washed porcine platelets to the sodium salts of stearic, oleic, palmitic, and myristic acids was analyzed turbidometrically. The fatty acids were prepared as aqueous suspensions and as taurocholate- or albumin-solubilized systems. The final concentration of fatty acid in the platelet preparation varied between 70 and 600 microM. This range was within or below the normal physiological limits of 300-1200 microM. Platelet aggregation was observed with both the suspended and taurocholate-solubilized fatty acids. The extent of platelet aggregate formation increased with the fatty acid concentration and chain length. With the exception of stearate, the taurocholate-solubilized fatty acids were more active than the suspensions. Albumin-solubilized fatty acids were devoid of platelet aggregating activity. Particle-size analysis of the solubilized fatty acids indicated that fatty acid precipitation had occurred subsequent to the addition of taurocholate-solubilized fatty acids to the platelets. This precipitation did not occur with the albumin-solubilized systems, suggesting that the fatty acids must assume a particulate physical state to induce aggregation. Platelet aggregation induced by fatty acids was not inhibited by 80 nM epoprostenol, 75 microM alprostadil, or 150 microM indomethacin. This finding indicated that the fatty acid-induced platelet aggregation was independent of cyclic AMP-related calcium shift, cyclooxygenase-arachidonate, or granular nucleotide release mechanisms.