Flunarizine (Flu), a difluoro derivative of cinnarizine, is well known as a calcium channel blocker. Recently, many authors have reported an antiepileptic effect of this drug in experimental models of epilepsy and in the clinical use. In the present study, acute effect of Flu was examined in the amygdaloid kindled cats, and add-on effects of Flu with valproic acid (VA) was also studied. Twenty three cats were used in this study. Amygdaloid kindling was established as previously reported. A strength of stimulations for kindling was at 300 microA. Same strength was used after completion of kindling. In this "high intensity" kindling, daily stimulation invariably induced initial amygdalo-hippocampal seizures followed by secondarily generalized seizures after completion of kindling. In addition, one amygdaloid stimulation was given daily for 5 days after completion of kindling in order to make it certain to induce secondarily generalized seizures. Drugs were injected on the 6th day intraperitoneally one or two hours before the stimulation daily given for 5 days after completion of kindling (GS 6) or after 4 days clearance period of previous administration of the drug. Pretreatment with Flu (high doses: 30 or 50 mg/kg, i.p.) abolished the secondary generalization after the GS 6. With this high doses of Flu animals died of side effect within 3 days after intraperitoneal administration. With lower doses of Flu less than 3 mg/kg, i.p. of Flu no side effect was encountered but antiepileptic effect was not obtained as well. Then add-on trials of Flu were performed with valproic acid (VA). The most effective combination was 100 mg/kg, i.p. of VA with 3 mg/kg, i.p. of Flu. With this combination, secondary generalization was suppressed at a ratio of 54.5% The results confirmed antiepileptic effect of Flu and add-on effect of Flu to VA.(ABSTRACT TRUNCATED AT 250 WORDS)