BACKGROUND: Since fibrin formation is an expression of the response of the host to parasite spread, the lipophosphoglycan (LPG) of Leishmania donovani and its carbohydrate fragment (PG) were examined for their capacity to inhibit procoagulant activity (PCA) production by human mononuclear cells stimulated with Escherichia coli endotoxin in vitro. METHODS: the putative inhibitory effect of LPG and its PG fragment was evaluated on the basis of their in vitro capacity to prolong significantly the time required for coagulation induced by endotoxin-stimulated mononuclear cells. RESULTS: LPG exhibited the most inhibitory activity, whereas the carbohydrate domain was not effective. These results are in agreement with the notion that LPG (but not PG) has an inhibitory effect on protein kinase C activity which plays a key role in the production of PCA by human monocytes. CONCLUSIONS: From a pathophysiological point of view, these data suggest the possibility that Leishmania avoids fibrin entrapment in the host through this inhibitory mechanism.