A transient increase in collagen VI expression precedes the accumulation of collagen I associated with interleukin-4 (IL-4)-induced mineralization in human osteoblast-like cells. Transfection with an antisense oligonucleotide specific for alpha1(VI) collagen mRNA was shown to attenuate mRNA levels of collagens VI and I. Incubating IL-4 treated cells with anti-collagen VI antiserum decreased expression of alpha1(I) mRNA. The results suggest that collagen VI may regulate collagen I expression in the early phase of IL-4-induced mineralization.