This study was conducted to examine empirically, the effects of macroeconomic variables like money supply, interest rate, investment and inflation rate on the Gross Domestic Product of Nigeria for the period 1970 to 2009. These macrovariables could be manipulated to control the economy to achieve macroeconomic equilibrium and hence economic growth. The econometric methods of unit root test, cointegration test, error correction mechanism and Granger causality test were used to analyse the secondary data sourced from the Central Bank Statistical Bulletin, volume 22, December, 2011. Both the error correction results and the Granger Causality results complement each other. With the exemption of interest rate all the regressands were properly signed but none of them was statistically significant. The poor performance of these variables was reflected in the low values of the R2 (0.358089) and F-statistic (3.681796). The positive value of the coefficient of the ECM-1 variable of 0.415208 indicates that the GDP was above its equilibrium value and so must be falling in the next period towards its equilibrium value with the speed of adjustment of 0.415208 or at the rate of 41.5% per period. The result of the Granger causality test indicates bilateral causation between inflation and interest rates, as well as between interest rate and investment. It also indicates unidirectional causation from money supply to inflation and investment and from GDP to money supply and investment, money supply to investment, interest rate to GDP, inflation to GDP. Finally it also indicates independence causation between money supply and interest rate, inflation and investment. The bilateral causation between interest rate and inflation rate is very strong and they are the major cause of the poor performance of the economy. It is highly recommended that the two of them should be reduced to their threshold one digit rate of between 5-7% each.