Abstract: Methods for stimulating gamma globin gene expression in a mammalian cell comprising contacting the cell with a compound selected from valeric acid and certain isomers, derivatives or salts thereof, including isovaleric acid, 4-pentynoic acid and methylthioacetic acid, or an inhibitor of a short chain fatty acyl CoA dehydrogenase, or an activator of protein kinase C are disclosed. The methods of the invention are particularly useful for ameliorating .beta.-globin disorders, such as sickle cell anemia or .beta.-thalassemia. The method of the invention can also be used to prevent or ameliorate malaria in a mammal. The compounds of the invention can also be used to stimulate differentiation of a cell. Pharmaceutical compositions of the active compounds of the invention are also disclosed.