On the basis of an initial case, we hypothesized that IgG4-positive plasma cells may be increased in pulmonary nodular lymphoid hyperplasia (PNLH) compared with other lymphoid proliferations of the lung. Six cases of PNLH, 9 cases of low-grade B-cell lymphoma of the bronchus-associated lymphoid tissue (BALT), 8 cases of intraparenchymal lymph nodes, 8 cases of either primary or secondary follicular bronchiolitis, and 4 cases of lymphocytic interstitial pneumonitis were stained by immunohistochemical analysis for IgG4 and IgG. The mean number of IgG4-positive and IgG-positive plasma cells and the IgG4/IgG ratio were determined from a manual count of images from 3 separate high-power fields (hpf) of areas showing the highest numbers of stained cells, respectively. The mean number of IgG4-positive plasma cells and the IgG4/IgG ratio were significantly increased in PNLH (IgG4=78/hpf, IgG4/IgG=0.35) compared to low-grade lymphoma of BALT (IgG4=4/hpf, P=0.02; IgG4/IgG=0.03, P=0.005), intraparenchymal lymph nodes (IgG4=7/hpf, P=0.03; IgG4/IgG=0.06, P=0.007), follicular bronchiolitis (IgG4=0/hpf, P=0.02; IgG4/IgG=0, P=0.004), and lymphocytic interstitial pneumonitis (IgG4=2/hpf, P=0.02; IgG4/IgG=0.06, P=0.007). These findings support our current understanding of PNLH as a distinct form of reactive lymphoid proliferation, potentially aid in its distinction from low-grade B-cell lymphoma of BALT, and raise the possibility that PNLH may belong within the family of IgG4-related sclerosing diseases.