The effect of lithium pretreatment on superoxide anion production and intracellular free calcium levels was investigated in polymorphonuclear leukocytes (PMN) from middle-aged and old individuals after stimulation by elastin peptides or FMLP. K-elastin (KE) significantly stimulated the production of superoxide anion by PMNs from middle-aged subjects, while this stimulation decreased with age and was absent in PMNs of elderly arteriosclerotic patients. Li pretreatment slightly increased this stimulating effect of KE in PMNs from middle-aged subjects and elderly arteriosclerotic patients, while slightly decreased in healthy elderly subjects. Moreover, Li was able to increase superoxide anion production even in the absence of KE, but this effect decreased also in PMNs of healthy and arteriosclerotic elderly patients. FMLP significantly increased superoxide anion production in all age-groups, but this effect was further amplified by Li only in PMNs of middle-aged subjects. In aged individuals Li pretreatment slightly decreased the effect of FMLP and had no effect in arteriosclerotic patients. Ca-mobilization induced by KE was inhibited by Li pretreatement in each age group. This inhibition by Li was much weaker in FMLP-stimulated PMNs. Li pretreatment did however modify the shape of the Ca-transient curves in FMLP stimulated leukocytes suggesting a qualitative modification of ion channel regulation. No such shape change of Ca-transient curves was observed after KE stimulation of Li pretreated PMNs. It appears that the regulation of these two receptors is differently affected by Li treatment.