Hybrids of the model BSA protein and layered silicate clay with d spacing of approximately 62 A were prepared from either direct or stepwise intercalation. The pristine montmorilloinite (Na+-MMT) was first modified by poly(oxyalkylene)-amine salts (POP- and POE-amine) of 2000 g/mol Mw to a gallery-expanded silicate (d spacing=53 and 18 A, respectively), which became accessible for BSA protein embedding. Subsequent BSA substitution allowed the embedding of the protein into the layered clay galleries in an uncompressed conformation. The stepwise process of embedding large molecules into the silicate gallery provides a new method for synthesizing biomaterial/clay hybrids potentially useful in drug delivery or biomedical design.