Reactions after booster injections of human diploid cell rabies vaccine (HDCV) were investigated to determine the possibility of IgE-type antibody involvement. Although normal manufacture of HDCV involves the inactivation of the virus with beta-propiolactone (BPL), the effect of BPL on nonviral vaccine components, such as host cell components or stabilizing proteins, may be typical of the haptenic action of small molecular weight chemicals. Specific IgE to commercial HDCV preparations, BPL-treated preparations of noninfected host MRC5 cell sonicate (BPL-MRC5), and a human albumin (HA) (BPL-HA) used as a stabilizing agent were detected in sera from five individuals who reported reactions after booster doses of HDCV. However, these patients had no detectable IgE to normal HA. Sera from nonvaccinated individuals, vaccinated individuals who reported no reaction after HDCV booster, and pollen-allergic individuals had no detectable IgE to HDCV, BPL-MRC5, or BPL-HA. Changes in the ratios of pre- to postbooster serum levels of specific IgE to HDCV and BPL-HA were significantly different in a group of 19 individuals who reported reactions to HDCV boosters; these changes in pre- to postbooster IgE levels in nonreactive vaccinees were not significant. Prebooster serum IgE RAST ratios to HDCV or BPL-HA were not predictive of potential reactions to HDCV. A number of experimental BPL-HA reaction mixtures were assayed to examine the effect of variable concentrations of BPL to HA. Increasing relative molar concentrations of BPL to HA resulted in increased electrophoretic mobility, whereas the highest relative specific IgE binding was detected in BPL-HA molar reaction mixtures of approximately 12.5:1.(ABSTRACT TRUNCATED AT 250 WORDS)