Protocols were evaluated in an attempt to produce human monoclonal antibodies (HumAb) specific for the human immunodeficiency virus type 1 (HIV-1). The first series of experiments involved in vitro immunization of normal human peripheral blood lymphocytes (PBL) with peptides C57 (HIV-1 strain IIIB clone BH10 gp 120 amino acids 324-338: GNMRQAHCNISRAKW) followed by either fusion to mouse/human heterohybrids or transformation with Epstein Barr virus (EBV). Using the hybridoma technology, three IgM class (lambda light chain) HumAb were obtained. In a parallel study, PBL from two HIV-1-infected patients were immortalized after in vitro stimulation with fragments of the HIV-1 envelope glycoprotein (recombinant gp120, the PB1 fragment of gp120, amino acids 295-473, or the penv9 fragment of gp160, amino acids 474-757). Five IgG class HumAb (three IgG2, lambda; one IgG1, K; one IgG3, lambda) reactive with the antigens used in the in vitro stimulations were obtained.