Expression of specific bacterial genes is differentially regulated during persistent, vs. active, chlamydial infection. Transcript patterns were examined using real-time reverse transcriptase-PCR in four in vitro models of persistence for Chlamydia pneumoniae strain CWL 029, using HeLa cells and normal human monocytes as host. Differential expression of genes encoding cell division proteins was variable when persistence was induced by interferon-gamma, penicillin G, or deferoxamine mesylate treatment, and in the monocyte model of persistence. Expression of genes encoding hsp60s and those specifying sigma-factors also was variable among models. These in vitro observations indicate that chlamydial persistence is not characterizable by a single transcript profile under all circumstances, supporting the idea that persistent infection in vivo is a complex, flexible strategy that promotes long-term survival of these organisms. Each model system studied here can provide information regarding the molecular characteristics of persistent C. pneumoniae infection. However, we do not know which aspect(s) of which model correspond to in vivo disease or other contexts.