This study aimed to measure IgG reactivities to DNA-free nucleosome subparticles (H2AH2B, H3H4) and nucleosome subparticles (H2AH2B-DNA, H3H4-DNA) and to evaluate the temporal relation of these reactivities, as well as those to single core histones, with iridocyclitis (IC) in patients with antinuclear antibody positive (ANA+) pauciarticular juvenile chronic arthritis (JCA). Reactivities to nuclear substrates were determined by enzymatic immunoassays in 120 sera from 45 children with ANA+ pauciarticular JCA. Significantly elevated IgG levels to H3 and H4, to DNA-free nucleosome subparticles, and to the nucleosome subparticle H3H4-DNA were present in patients with ANA+ pauciarticular JCA; no evidence of recognition of conformational epitopes was found. In both horizontal and follow-up studies, no relation between the reactivities studied and the development, presence, or history of IC was found. Our results show the absence of a relation of antibodies to histone molecules or to nucleosome subparticles with IC in patients with ANA+ pauciarticular JCA.