The molecular epidemiology and genetic diversity of the human metapneumovirus (hMPV) were characterized for a 3-year period (2000-2002) from viruses that were identified in South Africa. Two major genetic groups (A and B) and 2 subgroups (1 and 2) of hMPV were identified, as well as 2-6 possible genotypes within the subgroups. A shift in the predominant group was documented in successive seasons. Whereas the F gene was relatively conserved between subgroups, a high degree of variation was observed in the extracellular domain of the G gene of the virus. The G protein identities between groups A and B were 45.1%-53.1% at the nucleotide level and 22.4%-27.6% at the amino acid level. These results provide evidence for the diversity of both surface glycoproteins of hMPV in Africa, which may be a prerequisite to understanding protective immunity against hMPV.