Sympathetically innervated, isolated rabbit hearts were perfusated according to Langendorff and the nerves were stimulated at 2, 5 or 10 Hz by equally long trains of pulses. The outflows of prostaglandin-like substances (PLS) and of noradrenaline (NA), induced by the nerve stimulations, were followed. The sensitivity of the process of NA release to exogenous PGE1 (2--6 X 10--8 M) at 2, 5 and 10 Hz was assayed. The outflow of PLS was found to be frequency-dependent, being greater at 2 Hz than at higher discharge rates, while the outflow of NA was similar at the different frequencies. The inhibitory action of PGE1 on the NA release process was more pronounced at 2 than at 10 Hz. It is concluded that the frequency-dependence of the endogenous PGE-mediated inhibition of the release of NA from discharging sympathetic nerves is based on 2 independent, frequency-related mechanisms: a) a higher synthesis rate of PLS/impulse, and b) a more pronounced sensitivity of the process of NA release, at low compared to higher impulse frequences.