What kind of application do you have there ? Java, Net ?
Have you checked the DB log, listener log, CRS log ?
What is the error message? Use SQLPLUS from application server and try to connect and let us know the error message you are facing.
What error does the application report when attempting the connection ?
Have you tried with sqlplus on the application server ?
Has there been a change to DNS lookup / caching ? Can you try nslookup from the application server ?
Hemant K Chitale