To assess the role of platelets in thrombohemorrhagic complications of acute respiratory failure (ARF), we studied platelet function in 13 ARF patients admitted for intensive care, in six acutely ill intensive care patients without evidence of acute lung injury (non-ARF), and in 10 normal subjects. Platelet counts in ARF and non-ARF patients were similar to the normal range. The bleeding time of the ARF patients (8.5 +/- 0.9 min) was significantly longer (p less than 0.01) than the normal (4.8 +/- 0.2 min) but similar to non-ARF patients (5.4 +/- 0.8 min). The bleeding time prolongations in ARF patients were unrelated to platelet concentration. Platelet aggregation induced by ADP and thrombin was normal in both ARF and non-ARF patient groups. The epinephrine response was impaired in one non-ARF patient and in three ARF patients; collagen-induced aggregation was absent in two ARF patients, with a prolonged bleeding time. Levels of VIII:C and vWF in both groups of patients were similar to the normal level, but VIIIR:Ag levels in ARF patients (407 +/- 45% of normal) were higher (p less than 0.01) than in both non-ARF patients (210% +/- 10%) and normal subjects (106% +/- 4). The electrophoretic mobility of VIIIR:Ag was abnormal in ARF patients. The prolonged bleeding time in ARF patients appears to result from the qualitative and quantitative VIIIR:Ag defect. beta-Thromboglobulin levels were greater (p less than 0.01) in ARF patients (87.6 +/- 6.9 ng/ml; p less than 0.001) than in non-ARF patients (46.2 +/- 3.1 ng/ml) or in normal subjects (25.3 +/- 2.5 ng/ml p less than 0.0001). However, platelet factor 4 plasma levels in ARF patients (18 +/- 1.6 ng/ml) did not differ from those in non-ARF patients (15.0 +/- 3.0 ng/ml), but both were significantly different from normal (6.1 +/- 0.8 ng/ml). Plasma thromboxane B2 (T X B2) levels were not different from normal values in either ARF or non-ARF patients, but 6-keto-PGF1 alpha levels were significantly reduced (p less than 0.01) in ARF patients (215 +/- 43 pg/ml) compared to normal values (381 +/- 34 pg/ml). Non-ARF patients had 6-keto-PGF1 alpha levels (285 +/- 111 pg/ml) midway between the normal values and those of ARF patients. Our results suggest that in vivo platelet activation occurs in ARF. ARF patients have quantitative and qualitative platelet defects that may contribute to thrombotic and hemorrhagic complications.