The ability of Leu-enkephalin (LENK) to alter random migration of mouse spleen cells was tested in vitro and in vivo. Incubation of the cells with LENK (10(-14) M-10(-7) M) for 1 h at 37 degrees C suppressed the migration. The dose-response was irregular, showing two peaks in the physiological concentration range: 10(-10) M, and 10(-13)-10(-14) M. Intraperitoneal (i.p.) injection of LENK (7.5 mg/kg body wt) depressed the migratory capacity of the splenocytes harvested 2 and 24 h later. In contrast to the inhibitory effect of LENK on the migration of native cells, its effect on cells pretreated with the cAMP-elevating agents theophylline, 3-isobutyl-1-methyl-xanthine (IBMX) and forskolin was predominantly a stimulatory one. The addition of LENK resulted in attenuation or even full reversion of the migration-inhibition caused by those agents. Occasionally, potentiation of the suppression was also observed. There was no discrimination between the phosphodiesterase (PDE) inhibitors IBMX and theophylline, and the adenylate cyclase activator forskolin. Specificity of LENK effects was tested by using naloxone (10(-6) M), an opioid-receptor antagonist. Migration-inhibition induced by LENK was reversed in about two-thirds of the experiments. In contrast, migration-inhibition induced by cAMP-elevating agents, could not be reversed by naloxone. Naloxone itself was not inert, usually suppressing the locomotor ability of splenocytes. The data suggest that LENK-induced modulation of cell migration is (at least partly) mediated via opioid receptors.(ABSTRACT TRUNCATED AT 250 WORDS)