1. Parameters affecting the binding of the tricyclic drugs imipramine and 3-chloroimipramine to Giardia lamblia trophozoites were studied. 2. Two to three times more chlorimipramine than imipramine was bound, consistent with a similar difference in suppressing parasite growth (Weinbach et al., 1985). 3. Kinetic analysis and the ease with which bound drugs can be washed out of the parasites indicate that noncovalent forces are involved in the drug-parasite interaction. 4. Evidence is presented that such drugs probably bind to parasite protein at common binding sites. 5. The data relate to our earlier observation that chlorimipramine is about ten times more effective than metronidazole (Crouch et al., 1986) in suppressing G. lamblia growth in vitro. Tricyclic drugs, therefore, merit serious consideration as novel therapeutic agents against giardiasis.