The impact of plasma corticosterone levels on the sympathetic nervous system (SNS) response to intravenous lipopolysaccharide (LPS) or intracerebroventricular injections of PG was studied in anesthetized (urethan-chloralose) male Sprague-Dawley rats. For this, electrophysiological recordings of splenic and renal nerves were completed in control or adrenalectomized (ADX) rats. LPS (10 µg iv) similarly increased splenic and renal nerve activity in control rats with a shorter onset latency for the splenic nerve. Acute ADX enhanced the response of both nerves to LPS (P < 0.005) and reduced the onset latency of the renal nerve (P < 0.05). PGE₂ (2 µg icv) rapidly increased the activity of both nerves but preferentially (magnitude and onset latency) stimulated the renal nerve (P < 0.05). The magnitude of the splenic nerve response to PGE₂ was unaffected by ADX. Unexpectedly, PGE₂ was less effective at stimulating renal nerve activity in ADX animals relative to intact controls (P < 0.05). Pretreatment of ADX rats with a CRF antagonist {[D-Phe¹², Nle^21,38, C-MeLeu³⁷]CRF-(1241)} reversed this effect such that the renal nerve responded to central PGE₂ to a greater extent than the splenic nerve (P < 0.05), as was the case in non-ADX rats. These data indicate that enhanced sensitivity of central sympathetic pathways does not account for the enhanced SNS responses to LPS in ADX rats. Also, a CRF-related process appears to diminish renal sympathetic outflow in ADX rats.