We examine the relationship between the coherence of the knowledge base and the innovative performance of U.S. pharmaceutical firms during the 1990's. We develop measures of the coherence and scope of the firms' knowledge base. Count data regression models show a strong link between these two properties and the firms' innovative performance. Firms experience decreasing returns to scale in research but larger firms enjoy a significant size advantage in innovation. Knowledge flows are necessary in knowledge production but not sufficient to secure its quality. Over time, the contribution of the scope and coherence of the knowledge base is increasing.