Pituitary GH secretion is pulsatile in man and the rat, but evidence of pulsatility in the GH-dependent somatomedins (insulin-like growth factors) has not been described. In this study serum immunoreactive somatomedin-C periodicity was examined in 10 chronically cannulated unstressed rats. Blood samples were taken at 15-min intervals over 6 h, and serum rat GH and somatomedin-C measured by RIA. For somatomedin-C assay samples were first extracted into acidethanol to dissociate protein-bound peptide. Serum GH levels indicated episodic secretion, with a frequency of 2.85 Â± 0.24 h; some secretory episodes were polyphasic. The mean frequency of all GH spikes reaching 400 ng/ml or greater was 1.99 Â± 0.87 h. Somatomedin-C levels showed fluctuations over an average 2-fold concentration range, 0.60 Â± 0.20 to 1.21 Â± 0.29 U/ml (mean, 0.86 Â± 0.18 U/ml), with peaks occurring 1–1.5 h after most GH secretory peaks. The somatomedin-C peak frequency was 1.93 Â± 0.47 h. Summed GH values from 0–5 h were significantly correlated with summed somatomedin-C values from 1–6 h (r = 0.861, P = 0.0007), suggesting a 1-h lag between GH pulses and the following rise in somatomedin-C. Somatomedin-binding protein showed no regular fluctuations. This study indicates that serum somatomedin-C levels in unstressed rats show periodicity which may be directly related to pulsatile GH secretion.