Autoimmune pancreatitis (AIP) is a newly recognized disease. The presence of IgG4 positive plasma cells is thought to be of diagnostic help. In a surgical series of chronic pancreatitis cases, we determined the relative frequency of AIP before and after 1990, analyzed the diagnostic significance of IgG4 expression and examined the presence of oligoclonal T or B-cell populations. The histopathology of 202 surgical specimens of chronic pancreatitis removed between 1975 and 2004 was reviewed and 2 groups were distinguished, 1 of AIP cases and the other of nonautoimmune chronic pancreatitis (non-AIP CP). The intensity of infiltration of pancreatic tissue by IgG4 positive plasma cells and other immune cells was studied immunohistochemically. Finally, T and B-cell clonality was tested by polymerase chain reaction-based analysis. Except for 1 case in 1978, all cases of AIP were observed after 1990. IgG4 positive plasma cells were detected in 72.5% of AIP cases and in 63.1% of non-AIP CP cases. More than 20 cells per high power field were only seen in AIP (sensitivity 43%, specificity 100%). This finding was associated with higher age and grade. Polyclonal T and B-cell populations were found in both AIP and non-AIP CP except for 1 AIP case showing an oligoclonal IgGH-FR3 gene rearrangement. AIP seems to have increased considerably in frequency in the last 2 decades. High density infiltrates of IgG4 positive plasma cells are diagnostic for AIP, but are seen in less than half of the cases. T or B-cell oligoclonality could not be established as a feature of AIP.