Children with aCAH and those with PSC have similarly high levels of IgG, non organ and liver specific autoantibody & increased lymphocyte cytotoxicity to autologous hepatocytes. However, they differ in several immunological parameters. Only in aCAH there is decreased T suppressor cell number & function and increased circulating activated T helper cells, suggesting different mechanisms for the emergence of autoimmunity. Antinuclear antibody(ANA) is characteristic of both PSC and a sub-group of aCAH. The aim of this study was to characterise ANA in these 2 conditions. Using an indirect immunofluorescence technique and monoclonal antibodies to IgG subclasses, we have determined the immunoglobulin class and IgG subclass of ANA in 5 patients with aCAH[3 female, median age 18yrs, range 15-19yrs] & in 8 with PSC[4 female, median age 8.5yrs, range 3-14yrs]. Patients with aCAH had titre of ANA between 1:10 & 1:640 & in all of them ANA belonged to the IgG class and IgGl subclass. In contrast, in children with PSC ANA(titres 1:10-1:2560) were only IgG in 6 and IgG and IgM in 2. Of 6 patients with ANA titres of more than 1:10, 3 expressed ANA in 2 subclasses[IgGl & IgG3 in 2, IgGl & IgG4 in 1], and 1 patient expressed ANA in all 4 subclasses. These differences in ANA class & subclass between aCAH & PSC could derive from differences in the nature of the nuclear antigen or could indicate that ANA production results from the breakdown of different immunoregulatory mechanisms.