While attempting to evaluate CDS + and CD5 - anti-DNA-secreting plaque-forming cells (PFC) in patients with systemic lupus erythematosus (SLE), significant numbers of PFC against control sheep erythrocytes (ShE) treated with poly-L-lysine (PLL) but not further conjugated with single-stranded (ss) or double-stranded (ds) DNA were noted. Numbers of PFC obtained using PLL-ShE, ssDNA-ShE and dsDNA-ShE were not significantly different, all reactivity to DNA apparently being accounted for by binding of antibodies to PLL-treated ShE. Nevertheless, anti-PLL-PFC could be inhibited by soluble dsDNA included in the plaque assay. These findings might be explained by cationic anti-DNA antibodies binding non-specifically to anionic PLL. Control healthy subjects gave few PFC against PLL-ShE, ssDNA-ShE or dsDNA-ShE. Anti-PLL-PFC appeared to be related to disease activity, with higher numbers of both CD5 + and CD5 - PFC in patients with clinically active SLE.