Methods are described which utilize periodate-lysine-paraformaldehyde (PLP) as the only fixative for the investigation of nonfrozen small-bowel biopsy specimens by morphologic and immunohistochemical studies at both light and electron microscopic levels. Small-bowel biopsy specimens were obtained from children suspected of coeliac disease. In light microscopy, there was good morphology and haematoxylineosin staining of the mucosa. Immunofluorescence and immunoperoxidase staining of paraffin-embedded specimens enabled an accurate demonstration of immunoglobulins (IgA, IgM, IgG) in the duodenal mucosa. In conventional electron microscopy, PLP gave a reasonable preservation of ultrastructure. In immunoelectron microscopy, a pre-embedding immunoperoxidase technique provided exact ultrastructural localization of immunoglobulins. The methods are easy to adapt and they give reliable light and electron microscopic results.