Previous studies have shown that steroid hormones reduce concentrations of nerve growth factor (NGF) in medium conditioned by L-929 fibroblasts (L cells). In this study, we extend those observations and have measured in L cells the effects of hormone treatment on mRNA encoding NGF. L Cells were grown for 3 days in the presence or absence of hormones. NGF in conditioned medium was measured by NGF RIA; NGF mRNA was measured in cell extracts by Northern blot analysis. Cortisone reduced NGF levels in conditioned medium below the limit of detection of the RIA (less than 10% of control values) with an ED50 of 5 X 10(-9) M; NGF mRNA was reduced to 12% of control levels with an ED50 of 1 X 10(-8) M. Reductions in mRNA were maximal within 3 h and were completely reversed 12 h after removal of the hormone. Levels of NGF in conditioned medium were also undetectable in cultures treated with testosterone, and mRNA levels were reduced by 80%; the ED50 for both effects was 4 X 10(-9) M. Aldosterone (1 X 10(-6) M) reduced NGF to below detectable levels and NGF mRNA by 70%. Progesterone and thyroid hormone had no effect on NGF or NGF mRNA. 17 beta-Estradiol reduced levels of NGF in medium by 50%, but had no detectable effect on levels of NGF mRNA. These results suggest that cortisone, testosterone, and aldosterone decrease NGF levels in L cell-conditioned medium by reducing the cellular content of NGF mRNA.