Shiitake mushrooms [Lentinula edodes (Berk.) Pegler] have several therapeutic effects such as antibiotic, immunoregulatory, hypocholesterolemic, and hypotensive. Human studies have proven that serum cholesterol can be lowered by consuming shiitake mushrooms on a regular basis. However, few studies have evaluated shiitake mushroom effects for more than a few weeks. In this study, male spontaneously hypertensive rats were divided into six groups. Each group received one of the following diets: 0% cholesterol (C); C + 5% shiitake mushrooms; C + 5% Agaricus bisporus (Lange) Imbach; 1% cholesterol (1C); 1C + 5% shiitake; 1C + 5% A. bisporus. Serum cholesterol was measured at the end of 9 weeks and systolic blood pressure was measured weekly for 6 weeks. At the end of the study, total serum (TC) and very low-density lipoprotein (VLDL) cholesterol (mg·dL–1) were significantly lower in both of the shiitake diets compared to 1C or 1C + 5% A. bisporus. The total cholesterol for diets 1 through 6 were 44, 34, 36, 71, 34, and 54 mg·dL–1, respectively. Systolic blood pressure was significantly lower over the 6-week period for the shiitake and A. bisporus amended diets. The addition of cholesterol to the diets did not significantly affect systolic blood pressure. Results of this study indicate that both shiitake and A. bisporus mushrooms may help reduce hypertension. Shiitake mushrooms may be superior to white mushrooms for hypocholesterolemic effect when cholesterol in the diet is high. The results of this study reinforce other work conducted in Japan on animals and humans. Promotion of shiitake mushrooms as a product that can reduce cholesterol or blood pressure can increase sales if scientific information supports these claims.