Costal cartilage activity ([35S]sulphate and [3H]thymidine incorporation) and somatomedin (SM) activity in normal Snell-mice and dwarfmice before and during treatment with human growth hormone (hGH), porcine growth hormone (pGH) and L-thyroxine (T4) were studied, in order to obtain more insight in the interrelationship of these parameters with growth velocity. In normal mice endogenous (21 h incubation in medium with label) and plasma stimulated cartilage activity (21 h pre-incubation in medium, 48 h incubation with 20% human plasma, supplemented for the last 24 h with label) slows down immediately after birth, whereas the length velocity has a peak at 1 1/2 week of age and diminishes gradually thereafter. The endogenous activity of dwarfmice between the ages of 7 and 17 weeks is comparable with 3 weeks old normals, however plasma stimulated activity is much higher indicating a discrepancy between growth capacity of the cartilage and chronological age. Cartilage of dwarfmice recognizes growth hormone dependent differences in human plasma. The SM content of mouse serum using homologous cartilage turned out to be low for dwarfs, reaching subnormal values during hGH treatment. Three days after initiation of treatment with hGH endogenous sulphate and thymidine incorporation in costal cartilage is increased compared to saline treated dwarfmice. The effect is age-dependent and a combination of GH and T4 shows an effect equal to the sum of the effects of hormones given separately. After treatment for 5 weeks with hGH no differences between treated and untreated animals could be observed anymore, although the length velocity did not change throughout the 10 weeks of treatment. A difference of the cartilage sensitivity to human plasma between hGH treated and untreated mice is noted one week after treatment and a small difference remains after 5 weeks of treatment.