Oyster mushroom (Pleurotus ostreatus) is an important and is a good source of proteins, vitamins and minerals. In Pakistan local strains of mushroom are cultivated on various agricultural by-products as substrate. The widely used substrate for cultivation of the Oyster mushroom in Asia is rice straw. Keeping in view, its importance as a good source of energetic product having high protein value, the present studies were conducted to investigate the yield of exotic strains on cotton waste alone and were compared with amended rice husk under our natural environmental conditions. It was found that cotton waste + rice substrate gave the maximum yield of edible mushroom with the strain P. (sajor-caju) pulmonarious (WC-537) as compared to the substrate applied alone.