In an attempt to identify parasite antigen-specific antibody isotype(s) mediating inhibition of growth in vitro, we tested unfractionated sera and their corresponding purified antibody isotype-containing fractions in in vitro assays with asexual-stage parasites of Plasmodium falciparum in the presence or absence of monocytes. Using affinity purification techniques we fractionated individual and pooled serum samples from semi-immune Gabonese adults, to obtain samples containing either IgG1, 2, 3, and 4, IgG1, 2, and 4, or IgG3 alone, and a non-IgG fraction. Antibodies were quantified spectrophotometrically and the presence of different isotypes in individual fractions was confirmed by protein gel electrophoresis. In the absence of monocytes, we observed inhibition of parasite growth with whole serum and varying levels of either growth enhancement or inhibition with purified Ig-containing fractions. When used in a standardized assay of antibody-dependent cellular inhibition (ADCI) with a monocyte:infected erythrocyte ratio of 1:1, seven of eight serum samples inhibited growth to a mean level of 42%, and the different Ig-containing fractions displayed varying mean levels of inhibition: IgG3, 44%; IgG1--4, 22%; IgG1, 2, and 4, 10%; and non-IgG, - 10%. The results suggest that, among the different isotypes present in the serum of semi-immune individuals, parasite antigen-specific IgG3 in particular may play an important role in controlling parasitemia via an ADCI mechanism involving monocyte- derived mediators.