The effects of sterol biosynthesis inhibitors on growth and fine structure of Giardia lamblia PI strain cultures were analyzed. Azasterols demonstrated high efficacy in killing cells. The IC50 values for 22,26-azasterol and 24(R,S),25-epiminolanosterol were 7 mu M and 170 nM, respectively. Morphological analysis showed that azasterols induced changes in G. lamblia ultrastructure. The most significant alterations were: (a) considerable increase of the size of the peripheral vesicles, which are part of the parasite endosomal-lysosomal system; (b) appearance of autophagosomal structures; and (c) induction of differentiation, followed by an abnormal enlargement of encystation secretory vesicles. We propose that azasterols are effective chemotherapeutic drugs against Giardia lamblia in vitro and may have another target in cells besides sterol biosynthesis. (C) 2007 Elsevier Inc. All rights reserved.