Summary. The variation in immune responses to standard inoculation of the hepatitis-B virus vaccine suggest that host factors influence response in ways that are not presently understood. We studied 25 low/nonresponding health care workers (anti-HBs titer < 50 IU/1) after the third inoculation of an experimental hepatitis-B vaccine to determine their immune status (through lymphocyte phenotypes) and HLA type. After application of a fourth inoculation, the seroconverting subjects showed only low anti-HBs levels; three male subjects remained anti-HBs negative. Twelve months after the fourth inoculation only 9 of 25 subjects (36%) maintained anti-HBs titer >10 IU/1. Almost all subjects had normal B-cell and CD-4 and CD-8 counts and ratios. Relative to other European populations HLA-A-10 (P<0.05), B-12 ( P < 0.025), CW-5 (P<0.05), DR-3 (P<0.025), and DR-5 (P<0.025) were increased, whereas DR-2 (P<0.05) was decreased. However, after correction of the P-values for the number of HLA antigens determined, these differences were no longer significant. Furthermore, these HLA types were n o t the same as those reported in other studies (except for DR-3). We suggest that larger sample sizes or even not yet available immunogenetic markers wilt be required to prove a n " immunogenetic background" in low/nonresponders, if it exists.