Purpose:　Our　previous　works　suggested　that　sensitivity　of　neurons　with　chaotic　firing　patterns　to　stimuli　is　significantly　greater　than　that　in　neurons　with　periodic　firing　patterns,　which　shows　that　responsiveness　of　neurons　may　depend　on　the　complexity　of　the　firing　series.　This　study　was　performed　to　determine　the　relation　between　responsiveness　of　the　hippocampal　CA1　neurons　with　epileptiform　activity　(EA)　to　neurotransmitters　and　their　complexity　of　firing　series.　Methods:　Firing　series　of　CA1　neurons　were　recorded　extracellularly　in　rat　hippocampal　slice.　Approximate　entropy　was　used　to　describe　the　complexity　of　the　interspike　interval　(ISI)　series.　EA　was　induced　by　local　application　of　penicillin　(1,000　IU/ml).　The　change　of　firing　rate　induced　by　neurotransmitters　(glutamate　and　gamma-aminobutyric　acid)　was　compared　with　that　of　the　degree　of　complexity　of　ISI　series　in　the　process　of　EA.　Results:　The　excitatory　responses　to　glutamate　and　the　inhibitory　responses　to　gamma-aminobutyric　acid　in　CA1　neurons　appeared　to　be　decreased　during　the　process　of　penicillin-induced　EA.　However,　during　this　same　process,　the　approximate　entropy　of　the　ISI　series　also　was　decreased　significantly.　Conclusions:　The　results　suggest　that　the　reduced　responses　to　neurotransmitters　of　the　CA1　neurons　appear　to　be　closely　related　to　the　onset　of　EA.　Furthermore,　these　neurons　show　that　the　changes　in　responsiveness　are　closely　parallel　to　the　decrease　of　degree　of　complexity　of　firing　series　during　penicillin　epileptogenesis.