We compared growth rate and host-cell transcriptional responses of a Chlamydia trachomatis variant strain and a prototype strain. Growth dynamics were estimated by 16S rRNA level and by inclusion-forming units (IFUs) at different times after infection in HeLa cells. When inoculated at the same multiplicity of infection and observed 24-48 h after infection, the variant 16S rRNA transcriptional level was 3%-4% that of the prototype, and the IFUs of the variant strain were 0.1%-1% those of the prototype. Specific host-cell transcriptional responses to the variant were identified in a global-expression microarray in which variant strain-infected cells were compared with mock-infected and prototype strain-infected cells. In variant strain-infected cells, 47% (16/34) of specifically induced host genes were related to immunity and 32% (8/25) of specifically suppressed genes were related to lipid metabolism. The variant strain grew significantly more slowly and induced a modified host-cell transcriptional response, compared with the prototype strain.