Circulating plasmacytoid dendritic cells (PDC) decrease in human immunodeficiency virus (HIV) infection, either from loss or redistribution to lymph nodes (LN). Limited animal and human studies variably showed increased or decreased nodal PDC. CD123 immunostaining was performed on 28 archived LN biopsies (20 reactive) from 25 HIV patients. PDC clustering was graded (1: none; 2: rare small; 3: medium-sized, loose; and 4: large tight clusters) and correlated with HIV-lymphadenitis stage, blood CD4 counts, time since HIV diagnosis, and treatment duration. Increased PDC clustering was seen with decreasing CD4 counts (P = 0.001), shorter treatment duration (P = 0.0268), and advancing HIV-lymphadenitis stage (P = 0.06). No correlation with time since HIV diagnosis was noted. To our knowledge, this is the first human study assessing relationship of nodal PDC in HIV to CD4 counts, treatment duration, and lymphadenitis pattern. Our findings suggest that PDC redistribute to LN with advancing immunodeficiency and stage of HIV infection.