We previously reported a lod score of 2.3 suggesting linkage between panic disorder and the alpha-haptoglobin locus on chromosome 16q22 in 26 pedigrees. In the present study we tested for linkage between alpha-haptoglobin and panic disorder in 10 new pedigrees and excluded a gene for panic disorder from 6 centimorgans (recombination fraction, 0.06) surrounding the alpha-haptoglobin locus. The data were analyzed under a variety of assumptions about the transmission of panic disorder, and linkage was excluded by all genetic models but one. When lod scores from the present set of 10 pedigrees were pooled with those from the first 26, no evidence of genetic heterogeneity was found, and the maximum lod score was 0.67 at a recombination fraction of 0.17. Taken as a whole, the present findings do not support the presence of a disease gene for panic disorder closely linked to the alpha-haptoglobin locus on chromosome 16q22.