Mycobacterium tuberculosis strains associated with IS6110 restriction fragment-length polymorphism (RFLP) pattern clusters and strains demonstrating unique IS6110 RFLP patterns were investigated in interferon- gamma -activated THP-1 cells by measurement of binding, intracellular growth rate, and cytokine production. Binding was the same for all strains; however, strains from clusters grew significantly more rapidly than did unique strains. Maximal concentration of tumor necrosis factor (TNF)-alpha was detected at 2 days after infection, with unique strains eliciting significantly greater amounts than did strains from clusters. Interleukin (IL)-10 levels peaked at 1 day after infection with strains from clusters, whereas they peaked at 5 days after infection with unique strains. Rapid growth demonstrated by strains from clusters was highly correlated with rapid production of IL-10 and suppression of TNF-alpha in THP-1 cells during the early stages of infection. Characterization of this phenotype will further advance the investigation of virulence factors in M. tuberculosis.