5H-Oxazolo[4,5-b]phenoxazine (5) was synthesized by the reaction of 3-amino-2-hydroxyphenoxazine hydrochloride (2) with formamide. A series of styryl-oxazolophenoxazines (9) were prepared by condensation of 2-methyl-5-acetyloxazolo[4,5-b]phenoxazine methiodide (8) with aromatic aldehydes. By contrast, 2-aryl-oxazolophenoxazines (14) were synthesized by reaction of 3-aminophenoxaz-2-one (1) with the appropriate aldehydes in the presence of an acid–base catalyst. The biological activities of some of these compounds were tested.