The effects of chronic glucocorticoid stimulation and sympathetic innervation on myocardium developing in the absence of hemodynamic load were tested by grafting embryonic rat hearts into the anterior eye chamber (in oculo) of adult host rats. Myocardial grafts in control rats with normal hormonal milieu were compared with grafts in rats with chronic glucocorticoid stimulation (dexamethasone 40 µd) or glucocorticoid receptor type II blockade (RU 38486, 330 µd). Unilateral superior cervical ganglionectomy of one eye chamber prevented sympathetic innervation to one graft in each host. Two indices of growth, graft size (projected area) and terminal graft weight, were obtained. Dexamethasone treatment increased both size and weight of sympathetically innervated grafts, whereas RU486 treatment significantly decreased graft weight. Conversely, dexamethasone treatment decreased graft size in denervated eye chambers, whereas RU486 treatment had no effect. No differences in graft beating rate were observed among conditions. Sympathetic innervation modulated the effect of glucocorticoids on developing myocardium, suggesting that growth of sympathetically innervated myocardium is enhanced with glucocorticoid exposure, but growth of noninnervated myocardium (e.g. fetal heart) may be compromised by excessive glucocorticoid exposure. © 1995 International Pediatric Research Foundation, Inc.