In his recent review[1xDubremetz, J.F. Trends Microbiol. 1998; 6: 27–30Abstract | Full Text PDF | PubMed | Scopus (49)See all References][1], Dubremetz has succinctly summarized the highly effective process by which the protozoan parasite Toxoplasma gondii enters almost any cell type. One of the most fascinating aspects of invasion is that penetration is dependent on gliding motility of the parasite. Observational studies over many years and the elegant biochemical and molecular studies of Morisaki et al.[2xMorisaki, J.H., Heuser, J.E., and Sibley, L.D. J. Cell Sci. 1995; 108: 2457–2464PubMedSee all References][2]have shown that movement by the parasite is absolutely necessary for successful invasion and is dependent on an actin-based system[3xDobrowolski, J.M. and Sibley, L.D. Cell. 1996; 84: 933–939Abstract | Full Text | Full Text PDF | PubMed | Scopus (435)See all References][3]. Gliding motility is seen in bacteria, fungi, algae and many other protists, but the mechanisms responsible for producing movement over a substratum without deformation of the moving organism are as yet unexplained.Recently, Dobrowolski et al.[4xDobrowolski, J.M., Carruthers, V.B., and Sibley, L.D. Mol. Microbiol. 1997; 26: 163–173Crossref | PubMedSee all References][4]suggested that myosin is required for the gliding motility of T. gondii. Using an antibody raised to a conserved peptide sequence from the head domain of many myosin classes, they detected the presence of a low-molecular-weight myosin in T. gondii. This myosin appears to localize at the inner face of the parasite plasma membrane, where one might expect a motor for gliding motility to reside. Heintzelman and Schwartzman have identified three Toxoplasma myosin genes, which form a novel class that also includes a Plasmodium falciparum myosin[5xHeintzelman, M.B. and Schwartzman, J.D. J. Mol. Biol. 1997; 271: 139–146Crossref | PubMed | Scopus (80)See all References][5]. One of the T. gondii sequences predicts a 90-kDa protein that resembles the protein identified by the heterologous antiserum in Dobrowolski's studies. This myosin is unusually small and has a very short tail domain. The function of this interesting molecule has yet to be defined.The protein with which myosin interacts to transduce force across the plasma membrane also remains uncharacterized, but Dobrowolski et al.[4xDobrowolski, J.M., Carruthers, V.B., and Sibley, L.D. Mol. Microbiol. 1997; 26: 163–173Crossref | PubMedSee all References][4]suggest that the microneme protein MIC 2 (Toxoplasma microneme protein 2) might be a candidate. This protein is the T. gondii homologue of the malaria microneme protein TRAP (thrombospondin-related anonymous protein), which has been implicated in Plasmodium motility[6xSultan, A.A. et al. Cell. 1997; 90: 511–522Abstract | Full Text | Full Text PDF | PubMed | Scopus (392)See all References][6]. The kinase inhibitor KT5926, which both we [J.F.X. Wellehan and J.D. Schwartzman (1994) 47th Annual Meeting of the Society of Protozoologists, Cleveland, OH, USA, Abstr. T38] and Dobrowolski et al.[4xDobrowolski, J.M., Carruthers, V.B., and Sibley, L.D. Mol. Microbiol. 1997; 26: 163–173Crossref | PubMedSee all References][4]have shown inhibits T. gondii invasion, also inhibits MIC 2 release[4xDobrowolski, J.M., Carruthers, V.B., and Sibley, L.D. Mol. Microbiol. 1997; 26: 163–173Crossref | PubMedSee all References][4]. Further studies of the interaction of actin and the unusual T. gondii myosins and transmembrane proteins, such as MIC 2, are likely to shed light on the mechanism powering active host cell invasion.