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The mitogenic action of multiplication-stimulating activity (MSA) on normal mammalian chondrocytes has been examined. Addition of MSA (NIH, PkII-MSA, 2·5–500 ng/ml or Collaborative Research, CR-MSA, 50–250 ng/ml) to primary suspensions of chondrocytes prepared by enzymic digestion of costal and articular cartilage of rabbits (356–481 g body wt) resulted in a dose-dependent increase in [³H]thymidine incorporation into the trichloroacetic acid-precipitated cell contents. CR-MSA (50–250 ng/ml) also had a significant stimulatory effect on [³H]thymidine incorporation into human fetal chondrocytes (22 weeks of gestation) prepared by enzymic digestion. When PkII-MSA was added in the presence of 1·25% of a standard adult or cord plasma to either rabbit or human fetal (18 weeks) chondrocytes, the increase in [³H]thymidine incorporation appeared to be synergistic. The mitogenic action of MSA can thus be demonstrated on primary suspensions of mammalian chondrocytes. The action of MSA on human chondrocytes has not previously been reported.