We isolated and sequenced mouse lipocortin I cDNA clones from a lambda gt10 cDNA library prepared from Swiss 3T3 mRNA. The homology with human lipocortin I at the amino acid level is 86%. When confluent layers of Swiss 3T3 cells were stimulated with 10% fetal calf serum, expression of lipocortin I was strongly stimulated. In parallel, DNA synthesis was induced with a peak at 24 hours after glucocorticoid treatment indicating induction of cell proliferation. In the absence of serum glucocorticoid treatment provoked neither induction of DNA synthesis nor expression of lipocortin I. We conclude that serum contains an unidentified factor, which acts synergistically with glucocorticoids on cell proliferation and lipocortin I expression.