We studied the effect of high MW cartilage sulfation (somatomedin) inhibitors from rat liver on cartilage growth in vitro. Pelvic rudiments from 11-day-old chicken embryos (5.70 mg average weight) were incubated in an organ-culture system with defined tissue-culture medium; after two days (T0-2), media were changed and incubation continued for another three days (T2-5). Normal rat serum (10% vol/vol) stimulated cartilage growth (weight change + 1.33 +/- 0.16 mg, mean +/- SEM T0-2 and + 1.33 +/- 0.27 mg, T2-5). Partially purified cartilage sulfation inhibitors (CSI) caused a weight decrease (-1.09 +/- 0.17 mg T0-2 and -0.44 +/- 0.06 mg T2-5). Adding inhibitors to cartilage incubations containing normal serum abolished the growth-promoting effect of serum (-0.79 +/- 0.07 mg T0-2 and -0.40 +/- 0.08 mg T2-5). The growth-curtailing effect of CSI was reversible; after preincubating cartilage with CSI for two days (-0.62 +/- 0.11 mg T0-2), subsequently exposing it to normal serum allowed cartilage growth to resume (+1.02 +/- 0.21 mg T2-5). Cartilages incubated with normal serum and various concentrations of inhibitor exhibited a dose-dependent inhibition of serum-stimulated growth. Cartilage Length was not altered by the inhibitor; cartilage dry:wet weight ratio or protein concentration (microgram/mg wet weight) did not differ among groups. Triodothyronine (T3) stimulated cartilage growth in a dose-dependent manner as expected. Adding CSI to cartilage incubations containing T3 (1.5 nmol/l or 15 nmol/L) completely abolished the growth-stimulating effect of T3.(ABSTRACT TRUNCATED AT 250 WORDS)