Two potential malaria virulence factors, parasite multiplication rate (PMR) and red blood cell selectivity (measured as selectivity index [SI]), were assessed in Plasmodium falciparum clinical isolates from Mali and Kenya. At both sites, PMRs were low (Kenya median = 2.2, n = 33; Mali median = 2.6, n = 61) and did not differ significantly between uncomplicated and severe malaria cases. Malian isolates from hyperparasitemic patients had significantly lower PMRs (median = 1.8, n = 19) than other Malian isolates (uncomplicated malaria median = 3.1, n = 23; severe malaria median = 2.8, n = 19; P = 0.03, by Kruskal-Wallis test). Selective invasion occurred at both sites (Kenya geometric mean SI = 1.9, n = 98; Mali geometric mean SI = 1.6, n = 104), and there was no significant association between the SI and malaria severity. Therefore, in contrast to previous results from Thailand, we found no association of PMR and SI with malaria severity in African children. This raises the possibility of differences in the mechanisms of malaria virulence between sub-Saharan Africa and Asia.