The present study describes the first attempt to detect antisecretory activity in a lectin fraction of plasma from patients with acute diarrhea. The plasma antisecretory protein (ASP) was purified by affinity chromatography in agarose, and its antisecretory activity tested in rats subjected to intestinal challenge with cholera toxin. During the first 24 h of the diarrheal episode, antisecretory activity in patients (median 0, range 0-25%) was lower than that seen in the asymptomatic group (median 10, range 0-30%); 3 days later, when diarrhea ceased in most of the patients, the ASP activity increased significantly (median 30, range 0-75%). However, 5 days later the activity decreased again (median 0, range 0-55%). No differences in ASP levels were found between cases associated with an enteropathogen and those where no pathogen was identified. These findings reveal an inverse relationship between the increase in ASP and the patient's intestinal secretion; suggesting that ASP plays a role in the compensatory mechanisms that occur in diarrhea in humans.