Penicillin resistance in Neisseria spp is thought to be generated by the interspecies transfer of genetic material from naturally penicillin-resistant, commensal species. We examined a series of successive transformants with increasing levels of penicillin resistance, obtained by co-cultivation of Neisseria meningitidis derivatives with Neisseria polysaccharea. Our results suggest that, in addition to the well-known decrease in penicillin affinity of penicillin-binding protein-2 (PBP-2), decreased expression of the class 3 porin as well as decreased affinity of PBP-1 may contribute to higher level resistance of N. meningitidis to penicillin G and other beta -lactam compounds. (C) 2001 Elsevier Science BN. and International Society of Chemotherapy. All rights reserved.